title: ESCRT-III protein requirements for HIV-1 budding.
abstract: Two early-acting components of the cellular ESCRT pathway, ESCRT-I and ALIX, participate directly in HIV-1 budding. The membrane fission activities of ESCRT-III subunits are also presumably required, but humans express 11 different CHMP/ESCRT-III proteins whose functional contributions are not yet clear. We therefore depleted cells of each of the different CHMP proteins and protein families and examined the effects on HIV-1 budding. Virus release was profoundly inhibited by codepletion of either CHMP2 or CHMP4 family members, resulting in ≥100-fold titer reductions. CHMP2A and CHMP4B proteins bound one another, and this interaction was required for budding. By contrast, virus release was reduced only modestly by depletion of CHMP3 and CHMP1 proteins (2- to 8-fold titer reductions) and was unaffected by depletion of other human ESCRT-III proteins. HIV-1 budding therefore requires only a subset of the known human ESCRT-III proteins, with the CHMP2 and CHMP4 families playing key functional roles.
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Morita
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
authors.forename: Virginie
authors.initials: V
authors.lastname: Sandrin
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
authors.forename: John
authors.initials: J
authors.lastname: McCullough
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Katsuyama
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Baci Hamilton
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA. Electronic address: wes@biochem.utah.edu.
authors.forename: Wesley I
authors.initials: WI
authors.lastname: Sundquist
mesh_terms: D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development* / Q000472:pathogenicity; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D019065:Virus Assembly; D057074:Virus Release
chemical_list: C507674:CHMP2A protein, human; C503812:CHMP2B protein, human; C481529:CHMP4A protein, human; C478397:CHMP4B protein, human; C541008:CHMP4C protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D011994:Recombinant Proteins